tbuckley/cabot-search huggingface dataset:
Translating energy balance research from the bench to the clinic to the community: Parallel animal‐human studies in cancer
Authors: Miriam B. Garcia, Keri L. Schadler, Joya Chandra, Steven K. Clinton, Kerry S. Courneya, Zobeida Cruz‐Monserrate, Carrie R. Daniel, Andrew J. Dannenberg, Wendy Demark‐Wahnefried, Mark W. Dewhirst, Carol J. Fabian, Stephen D. Hursting, Melinda L. Irwin, Neil M. Iyengar, Jennifer L. McQuade, Kathryn H. Schmitz, Karen Basen‐Engquist
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal‐Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer toward practice changes. This review summarizes key topics discussed to advance research on the role of energy balance, including physical activity, body composition, and dietary intake, on cancer development, cancer outcomes, and healthy survivorship.
Impact of COVID-19 vaccination on COVID-19 hospital admissions in England during 2021: an observational study
Authors: Felicity Cornforth, Lucie Webber, Gabriele Kerr, Hywell Dinsdale, Azeem Majeed, Peter Greengross
Journal: Journal of the Royal Society of Medicine (2023)

Objectives To examine the impact of COVID-19 vaccination on hospital admissions in England in 2021. Design Observational study of emergency admissions for COVID-19 by vaccination status in people 16 years and over in England. Setting Hospitals in England. Participants A total of 48.1 million people registered with an English GP, aged ≥16 years with a recent NHS contact. Main outcome measures Emergency hospital admissions with a primary diagnosis of COVID-19 between 1 January and 31 December 2021. Monthly admission rates were directly standardised for age, sex, risk category and vaccination dose to estimate vaccine effectiveness (VE) over time, between vaccine doses, age groups and risk groups. Results A total of 192,047 hospital admissions were included. The unvaccinated admission rate was higher in December 2021 (6.1 admissions per 100,000 person-days; 95% CI: 5.9 to 6.3) than January 2021 (4.9; 95% CI: 4.9 to 5.0). Vaccinated admission rates were ≤1 per 100,000 from February to December. Doses 1 and 2 VE waned over time, particularly in older and clinically vulnerable groups (although this may reflect that they were vaccinated earlier). Dose 3 VE remained above 93%. Conclusions COVID-19 hospitalisations were consistently highest in the unvaccinated. Despite high case rates at the end of 2021, overall admission rates remained stable, driven by low admission rates among vaccinated people. There is population-level waning in VE, recovering after subsequent doses, potentially more marked in older and at-risk groups. The findings support JCVI (Joint Committee on Vaccination and Immunisation) guidance for an ongoing booster programme, especially in older people and higher clinical risk groups.
The evolving knowledge on primary hemostasis in patients with cirrhosis: A comprehensive review
Authors: Alberto Zanetto, Elena Campello, Marco Senzolo, Paolo Simioni
Journal: Hepatology (2023)

Patients with cirrhosis develop complex alterations in primary hemostasis that include both hypocoagulable and hypercoagulable features. This includes thrombocytopenia, multiple alterations of platelet function, and increased plasma levels of von Willebrand factor. Contrary to the historical view that platelet dysfunction in cirrhosis might be responsible for an increased bleeding tendency, the current theory posits a rebalanced hemostasis in patients with cirrhosis. Severe thrombocytopenia is not indicative of the bleeding risk in patients undergoing invasive procedures and does not dictate per se the need for pre-procedural prophylaxis. A more comprehensive and individualized risk assessment should combine hemostatic impairment, the severity of decompensation and systemic inflammation, and the presence of additional factors that may impair platelet function, such as acute kidney injury and bacterial infections. Although there are multiple, complex alterations of platelet function in cirrhosis, their net effect is not yet fully understood. More investigations evaluating the association between alterations of platelet function and bleeding/thrombosis may improve risk stratification in patients with decompensated cirrhosis. Besides hemostasis, the assessment of von Willebrand factor Ag and ADP-induced, whole-blood platelet aggregation normalized by platelet count (VITRO score and PLT ratio) are promising biomarkers to predict the risk of hepatic decompensation and survival in both compensated and decompensated patients. Further investigations into the in vivo interplay between platelets, circulating blood elements, and endothelial cells may help advance our understanding of cirrhotic coagulopathy. Here, we review the complex changes in platelets and primary hemostasis in cirrhosis and their potential clinical implications.
Effect of Epirubicin Plus Paclitaxel vs Epirubicin and Cyclophosphamide Followed by Paclitaxel on Disease-Free Survival Among Patients With Operable <i>ERBB2</i>-Negative and Lymph Node–Positive Breast Cancer
Authors: Peng Yuan, Yikun Kang, Fei Ma, Ying Fan, Jiayu Wang, Xue Wang, Jian Yue, Yang Luo, Pin Zhang, Qing Li, Binghe Xu
Journal: JAMA Network Open (2023)

Importance Adjuvant therapy is an important and effective treatment for breast cancer. However, there is a lack of head-to-head clinical trials comparing the regimens epirubicin plus paclitaxel (EP) vs epirubicin and cyclophosphamide followed by paclitaxel (EC-P) in breast cancer. Objective To evaluate the noninferiority of a cyclophosphamide-free (EP) regimen compared with the standard EC-P regimen for patients with operable hormone receptor–positive, ERBB2 (formerly HER2 )-negative, lymph node–positive breast cancer. Design, Setting, and Participants This prospective, open-label, phase 3, noninferiority randomized clinical trial was conducted from June 1, 2010, to June 30, 2016, in the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing. Patients with hormone receptor–positive, ERBB2 -negative, lymph node–positive operable breast cancer were included and randomized into 2 treatment groups. Data were analyzed from June 30, 2016, to November 1, 2022. Interventions Patients received adjuvant epirubicin (75 mg/m 2 ) and paclitaxel (175 mg/m 2 ) every 3 weeks for 6 cycles (EP regimen) or epirubicin (90 mg/m 2 ) and cyclophosphamide (600 mg/m 2 ) every 3 weeks for 4 cycles followed by paclitaxel (175 mg/m 2 ) every 3 weeks for 4 cycles (EC-P regimen) as the intention-to-treat (ITT) population. Main Outcomes and Measures The primary outcome was disease-free survival (DFS), and the secondary outcomes included overall survival (OS), distant DFS, and safety. Results A total of 900 patients were registered, and 813 eligible patients (median age, 48 [IQR, 41-56] years) were randomly assigned to the EP group (n = 407) or the EC-P group (n = 406) after the surgical procedure. Through a median follow-up of 93.6 (IQR, 60.9-114.1) months, the hazard ratio (HR) of DFS for EP vs EC-P was 0.82 (95% CI, 0.62-1.10; 5-year DFS, 86.0% vs 80.6%; noninferior P = .001). The 5-year OS for the ITT population treated with the EP or the EC-P regimen was 94.7% vs 95.0%, respectively (HR, 0.95 [95% CI, 0.61-1.49]). Patients in the EP group had more frequent toxic effect events than those in the EC-P group. Conclusions and Relevance In this prospective, open-label, phase 3, randomized clinical trial, the EP regimen was noninferior to the EC-P regimen. These findings supported that the EP regimen could be an effective adjuvant chemotherapy regimen for women with ERBB2 -negative breast cancer. Trial Registration ClinicalTrials.gov Identifier: NCT01134523
Printed Silk Microelectrode Arrays for Electrophysiological Recording and Controlled Drug Delivery
Authors: Nouran Adly, Tetsuhiko F. Teshima, Hossein Hassani, George Al Boustani, Lennart J.K. Weiß, Gordon Cheng, Joe Alexander, Bernhard Wolfrum
Journal: Advanced Healthcare Materials (2023)

The use of soft and flexible bioelectronic interfaces can enhance the quality for recording cells' electrical activity by ensuring a continuous and intimate contact with the smooth, curving surfaces found in the physiological environment. This work develops soft microelectrode arrays (MEAs) made of silk fibroin (SF) films for recording interfaces that can also serve as a drug delivery system. Inkjet printing is used as a tool to deposit the substrate, conductive electrode, and insulator, as well as a drug-delivery nanocomposite film. This approach is highly versatile, as shown in the fabrication of carbon microelectrodes, sandwiched between a silk substrate and a silk insulator. The technique permits the development of thin-film devices that can be employed for in vitro extracellular recordings of HL-1 cell action potentials. The tuning of SF by applying an electrical stimulus to produce a permeable layer that can be used in on-demand drug delivery systems is also demonstrated. The multifunctional MEA developed here can pave the way for in vitro drug screening by applying time-resolved and localized chemical stimuli.
Errors in Figure 3 and Supplement 1
Journal: JAMA Network Open (2023)

Jennifer Allen, ANP-BC, APHN-C; Selene S. Mak, PhD, MPH; Meron Begashaw, MPH; Jody Larkin, MS; Isomi Miake-Lye, PhD; Jessica Beroes-Severin, BA; Juli Olson, DC, DACM, DipOM; Paul G. Shekelle, MD, PhD
Evaluation of Systemic Treatments of Small Intestinal Adenocarcinomas
Authors: Tim de Back, Isabelle Nijskens, Pascale Schafrat, Myriam Chalabi, Geert Kazemier, Louis Vermeulen, Dirkje Sommeijer
Journal: JAMA Network Open (2023)

Importance Although small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of high-quality evidence, guidelines for colorectal cancer are often followed in the treatment of SIAs. Objective To review the current evidence regarding survival benefit of systemic therapies, including chemotherapy, targeted agents, and immunotherapy, for patients with SIAs. Data Sources Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, MEDLINE and Embase were searched for articles published from January 1, 2005, until June 1, 2022. Study Selection Retrospective cohort studies and prospective phase 2 or 3 trials describing survival after systemic therapies for patients with SIAs were eligible for inclusion. Assessment of study eligibility was blinded and performed by 3 reviewers. Data Extraction and Synthesis The reviewers independently extracted data. Random effects, inverse variance, pairwise meta-analyses were performed. Main Outcomes and Measures Primary outcomes were overall survival (OS) and progression-free survival (PFS) of patients with SIAs after systemic therapies. Measures of interest included hazard ratios for survival and median survival times. Results Overall, 57 retrospective cohort and phase 2 studies of 35 176 patients were included. Adjuvant chemotherapy, generally fluoropyrimidine-based, was associated with increased OS in stage I to III SIAs (hazard ratio [HR], 0.60; 95% CI, 0.53-0.68), especially in stage III tumors (HR, 0.55; 95% CI, 0.48-0.64), irrespective of tumor localization. Palliative chemotherapy was also associated with an OS benefit (HR, 0.48; 95% CI, 0.40-0.58). Fluoropyrimidine-oxaliplatin combinations were superior to other regimens (OS: HR, 0.54; 95% CI, 0.30-0.99; PFS: HR, 0.46; 95% CI, 0.30-0.71). Furthermore, bevacizumab added to chemotherapy compared with chemotherapy alone was associated with significantly prolonged PFS (HR, 0.62; 95% CI, 0.43-0.89). Immunotherapy showed a 50% overall response rate in previously treated defective mismatch repair tumors. Conclusions and Relevance In this systematic review and meta-analysis, adjuvant and palliative chemotherapy were both associated with improved survival of patients with SIAs, especially fluoropyrimidine-based regimens and fluoropyrimidine-oxaliplatin combinations. Adding bevacizumab to chemotherapy appears to prolong PFS and deserves further investigation. Immunotherapy seems beneficial and should be considered for patients with defective mismatch repair tumors. International collaborations should be undertaken to confirm and improve efficacy of systemic therapies for patients with SIAs.
Association between serum albumin and outcomes in heart failure and secondary mitral regurgitation: the <scp>COAPT</scp> trial
Authors: Kent Y. Feng, Andrew P. Ambrosy, Zhipeng Zhou, Ditian Li, Jeremy Kong, Jonathan G. Zaroff, Jacob M. Mishell, Ivy A. Ku, Andrea Scotti, Augustin Coisne, Björn Redfors, Michael J. Mack, William T. Abraham, JoAnn Lindenfeld, Gregg W. Stone
Journal: European Journal of Heart Failure (2023)
Intravenous iron in patients with heart failure and iron deficiency: an updated meta‐analysis
Authors: Fraser J. Graham, Pierpaolo Pellicori, Paul R. Kalra, Ian Ford, Dario Bruzzese, John G.F. Cleland
Journal: European Journal of Heart Failure (2023)

Abstract Aims For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta‐analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF. Methods and results We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all‐cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61–0.93; p &lt; 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53–0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70–1.05; p = 0.14) and all‐cause mortality (OR 0.93, 95% CI 0.78–1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow‐up, which was less disrupted by the COVID‐19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation &lt;20% (OR 0.67, 95% CI 0.49–0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74–1.30) (heterogeneity p = 0.07). Conclusion In patients with HF and ID, this meta‐analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all‐cause mortality remains inconclusive.
The Search for Genomic Biomarkers of Response to Immunotherapy in Ovarian Cancer
Authors: Duaa H. Al-Rawi, Nicole Rusk, Claire F. Friedman
Journal: Clinical Cancer Research (2023)

Immune checkpoint blockade has been ineffective in ovarian cancer, and there is an ongoing effort to identify biomarkers of therapeutic benefit. Despite promising preclinical data, a substudy of the IMagyn050 trial found that patients with homologous recombination deficient tumors did not have improved progression-free survival with the addition of the PD-L1 inhibitor atezolizumab. See related article by Landen et al., p. 1698.
Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis—A randomized controlled study
Authors: Lise Gether, Heidi Storgaard, Sanja Kezic, Ivone Jakasa, Bolette Hartmann, Kirsa Skov‐Jeppesen, Jens J. Holst, Anders J. Pedersen, Julie Forman, Gerrit van Hall, Ole E. Sørensen, Lone Skov, Mads A. Røpke, Filip K. Knop, Jacob Pontoppidan Thyssen
Journal: Allergy (2023)

Abstract Introduction Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption. Objectives We examined whether intensive daily whole‐body TCS treatment over 2 weeks followed by twice weekly application for 4 weeks could elicit insulin resistance and increase bone resorption in adults with AD. Methods A randomized parallel‐group double‐blind double‐dummy non‐corticosteroid‐based active comparator study design was completed in Copenhagen, Denmark. Thirty‐six non‐obese, non‐diabetic adults with moderate‐to‐severe AD were randomized to whole‐body treatment with betamethasone 17‐valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic‐euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after 2 weeks of daily treatment and after further 4 weeks of twice‐weekly maintenance treatment. Results AD severity improved with both treatments and systemic inflammation was reduced. After 2 weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone ( n = 18) and tacrolimus ( n = 18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both 2 and 6 weeks but remained unchanged in the tacrolimus arm. Conclusions Whole‐body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short‐term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS.
Long-term treatment outcomes in patients with multidrug-resistant tuberculosis
Authors: Christina Maier, Dumitru Chesov, Dagmar Schaub, Barbara Kalsdorf, Sönke Andres, Inna Friesen, Maja Reimann, Christoph Lange
Journal: Clinical Microbiology and Infection (2023)

To describe long-term treatment outcomes in patients with multi-drug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) and validate established outcome definitions for MDR/RR-TB treatment.Among patients with MDR/RR-TB admitted to a German MDR/RR-TB referral centre from 1 September 2002 to 29 February 2020, we compared long-term treatment outcomes derived from individual patient follow-up with treatment outcomes defined by WHO-2013, WHO-2021 and the Tuberculosis Network European Trials Group-2016.In a total of 163 patients (mean age, 35 years; standard deviation, 13 years; 14/163 [8.6%] living with HIV; 109/163 [66.9%] men, 149/163 [91.4%] migrating to Germany within 5 years), the treatment of culture-confirmed MDR/RR-TB was initiated. Additional drug resistance to a fluoroquinolone or a second-line injectable agent was present in 15 of the 163 (9.2%) Mycobacterium tuberculosis strains; resistance against both the drug classes was present in 29 of the 163 (17.8%) strains. The median duration of MDR/RR-TB treatment was 20 months (interquartile range, 19.3-21.6 months), with a medium of five active drugs included. The median follow-up time was 4 years (47.7 months; interquartile range, 21.7-65.8 months). Among the 163 patients, cure was achieved in 25 (15.3%), 82 (50.3%) and 95 (58.3%) patients according to the outcome definitions of WHO-2013, WHO-2021, and the Tuberculosis Network European Trials Group-2016, respectively. The lost to follow-up rate was 17 of 163 (10.4%). Death was more likely in patients living with HIV (hazard ratio, 4.28; 95% confidence interval, 1.26-12.86) and older patients (hazard ratio, 1.08; 95% confidence interval, 1.05-1.12; increment of 1 year). Overall, 101/163 (62.0%) patients experienced long-term, relapse-free cure; of those, 101/122 (82.8%) patients with a known status (not lost to-follow-up or transferred out) at follow-up.Under optimal management conditions leveraging individualized treatment regimens, long-term, relapse-free cure from MDR/RR-TB is substantially higher than cure rates defined by current treatment outcome definitions.
SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining
Authors: Benjamin Billot, Douglas N. Greve, Oula Puonti, Axel Thielscher, Koen Van Leemput, Bruce Fischl, Adrian V. Dalca, Juan Eugenio Iglesias
Journal: Medical Image Analysis (2023)

Despite advances in data augmentation and transfer learning, convolutional neural networks (CNNs) difficultly generalise to unseen domains. When segmenting brain scans, CNNs are highly sensitive to changes in resolution and contrast: even within the same MRI modality, performance can decrease across datasets. Here we introduce SynthSeg, the first segmentation CNN robust against changes in contrast and resolution. SynthSeg is trained with synthetic data sampled from a generative model conditioned on segmentations. Crucially, we adopt a domain randomisation strategy where we fully randomise the contrast and resolution of the synthetic training data. Consequently, SynthSeg can segment real scans from a wide range of target domains without retraining or fine-tuning, which enables straightforward analysis of huge amounts of heterogeneous clinical data. Because SynthSeg only requires segmentations to be trained (no images), it can learn from labels obtained by automated methods on diverse populations (e.g., ageing and diseased), thus achieving robustness to a wide range of morphological variability. We demonstrate SynthSeg on 5,000 scans of six modalities (including CT) and ten resolutions, where it exhibits unparallelled generalisation compared with supervised CNNs, state-of-the-art domain adaptation, and Bayesian segmentation. Finally, we demonstrate the generalisability of SynthSeg by applying it to cardiac MRI and CT scans.
MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Nonsquamous NSCLC Progressing On or After Checkpoint Inhibitor Therapy or Chemotherapy
Authors: Kai He, David Berz, Shirish M. Gadgeel, Wade T. Iams, Debora S. Bruno, Collin M. Blakely, Alexander I. Spira, Manish R. Patel, David M. Waterhouse, Donald A. Richards, Anthony Pham, Robert Jotte, David S. Hong, Edward B. Garon, Anne Traynor, Peter Olson, Lisa Latven, Xiaohong Yan, Ronald Shazer, Ticiana A. Leal
Journal: Journal of Thoracic Oncology (2023)

Sitravatinib, a receptor tyrosine kinase inhibitor targeting TYRO3, AXL, MERTK receptors, and vascular epithelial growth factor receptor 2, can shift the tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPIs) may augment antitumor activity.
Clinical and histopathologic features of pediatric longitudinal melanonychia: A multicenter retrospective study
Authors: Jongeun Lee, Jai Hee Bae, Se Jin Oh, Dongyoun Lee, Hee Joo Kim, Il-Hwan Kim, Je-Ho Mun, Kwang Ho Kim, Kyung Ho Lee
Journal: Journal of the American Academy of Dermatology (2023)
Novel use of lumen-apposing metal stent for recanalization of complete stenosis of colo-colonic anastomosis
Authors: Paul Guzik, Allison Aka, Wasseem Skef
Journal: Endoscopy (2023)

Combined antegrade-retrograde dilation [1] is an established technique that has been adapted for benign colonic obstruction [2] [3] but requires use of accessory devices and predilation followed by deployment of self-expanding metal stents [2] [3]. Rendezvous sigmoidorectal reanastomosis using a lumen-apposing metal stent (LAMS) has also been described with endosonographic (EUS) guidance [4]. We hereby report a recanalization of complete stenosis of a colo-colonic anastomosis without EUS guidance.